Every year, millions of Americans suffer tissue loss or end-stage organ failure. Approximately 8 million surgical procedures are performed annually in the United States to treat these disorders. Physicians treat organ or tissue loss by transplanting organs from one individual to another. Although transplantation is one of the life-saving therapies, it is seriously limited by donor scarcity. Tissue engineering, which aims at creating biological body parts as alternatives for transplants, offers the possibility of substantial savings by providing substitutes that are less expensive than donor organs and by providing a means of intervention before patients become critically ill (Langer and Vacanti, “Tissue engineering,” Science 260: 920-926 [1993]).
One approach for tissue engineering uses tissue-inducing substances. The success of this approach depends on the purification and large-scale production of appropriate signal molecules, such as growth factors, and, in many cases, the development of methods to deliver these molecules to their targets. Another approach uses isolated cells or cell substitutes. This approach avoids the complications of surgery, allows replacement of only those cells that supply the needed function, and permits manipulation of cells before infusion.
However, isolated cells cannot form new tissues on their own. Most cells have a requirement for attachment to a surface in order to replicate and function, and require specific environments which often include the presence of supporting material to act as a template for growth. Three dimensional scaffolds are used to mimic their natural counterparts, the extracellular matrices of the body. They serve both as a physical support and as an adhesive substrate (U.S. Pat. No. 5,514,378 to Mikos et al. [1996]). Thus, scaffolding plays a pivotal role in the engineering of new tissues and organs (Ma and Langer, “Methods for the fabrication of biodegradable polymer foams for cell transplantation and tissue engineering,” in Tissue Engineering Methods and Protocols, Yarmush and Morgan (eds.), Humana Press Inc.: Totowa, N.J., 1998).
Natural or synthetic polymers can be used to form highly porous scaffolds. Various tissues have been engineered from highly porous scaffolds prepared from synthetic biodegradable polymers such as poly(glycolic acid), poly(lactic acid), and poly(glycolic acid-co-lactic acid). (See e.g., Ma and Langer, supra; Ma et al., J. Biomed Mater. Res. 29: 1587-1595 [1995]; Ma et al., Ann. Thorac. Surg. 60: S513-516 [1995]; Cusick et al., J. Pediatr. Surg. 32: 357-360 [1997]; Ma et al., Transactions of the Society for Biomaterials 295 [1997]; Ma and Langer, “Degradation, structure and properties of fibrous nonwoven poly(glycolic acid) scaffolds for tissue engineering,” in Polymers in Medicine and Pharmacy, Mikos et al. (eds.), pp. 99-104, MRS: Pittsburg [1995]; Shinoka et al., Circulation 94 (9 Supplement): II-164-168 [1996]; Cao et al., Transplant Proc. 26: 3390-3392 [1994]; Kim et al., Transplant Proc. 29: 858-860 [1997]). Although synthetic polymers generally give good reproducibility and controlled release kinetics compared to natural materials (See e.g., U.S. Pat. Nos. 5,855,610 and 5,716,404 to Vacanti et al.), they may not interact with cells in a desired manner (Langer and Vacanti, supra). On the other hand, natural polymers are advantageous in that they contain information (e.g., particular amino acid sequences) that facilitates cell attachment or maintenance of differentiated function (Langer and Vacanti, supra).
What is needed is a method for controlling three-dimensional structures of hydrogel/cell constructs from natural polymers, for use as highly porous scaffolds that permit the support of cells for growth.